Breast cancer is the most common cancer in women. With growing numbers of breast cancer survivors, cancer treatment induced bone loss and bone fracture are becoming a major concern. Aromatase inhibitor (AI) is very succesful as an adjuvant therapy in estrogen positive postmenopausal women to prevent cancer progression. However, it also increases bone loss and suceptibility to fractures due to profound estrogen depletion. Early identification of patients at a high risk for bone loss, prevention, and frequent monitoring of treatment interventions are absolutely necessary to decrease the risk of bone fractures. The currently much-used method of monitoring bone mineral density (BMD) is neither sensitive to small changes in bone density, nor suitable for frequent assesments of bone density. We propose an innovative assay method to directly detect early changes in bone turnover, to be used for long-term monitoring purposes. We hypothesize that the 41Ca/Ca measurement in urine will offer (a) early detection of the accelerated bone resorption that result from the use of aromatase inhibitors, and (b) dynamic monitoring of the bone formation process due to antiresorptive drug intervention. Specific Aims:To determine the AI treatment response in pharmacokinetics (PK) of long-lived 41Ca and compare with BMD measurements, urine NTx levels, and serum PINP levels. To use the 41Ca assay to monitor the effects of bisphosphonate intervention on bone formation and to compare this to BMD measurements, urine NTx levels, and serum PINP levels. A microdose amount of 41Ca will be administered intravenously to all consented postmenopausal breast cancer patients. The urinary 41Ca assay will be characterized with and without AI interventionto establish the enhanced bone resorption in postmenopausal breast cancer patients. This assay will be further compared to DXA scans, urine NTx levels, serum PINP levels. PTH, complete blood metabolic tests and urine analysis will also be performed. After one year, patients who have low bone density (osteopenic and osteoporosis) determined from BMD measurements, will be treated with antiresorptive drugs. Biomarkers will be measured before and after this intervention and will be followed for one year. Breast cancer treatment induced bone loss can have tremendous negative effect on survivors'quality of life. Early identification of patients who are "fast bone losers" is essential. Early detection will allow an early intervention to prevent bone fracture. In addition, the ability to closely monitor the effects of intervention will allow adjustment of individual treatments as needed. Our method has the potential to be a clinically useful screening tool for breast cancer treatment management. This study will also offer researchers the opportunity to investigate the bone remodeling process directly. With an aging population, breast-cancer-treatment-induced bone loss can have a tremendous negative effect on breast cancer survivors and their quality of life [1-4]. Our objective is to develop a simple screening tool based on a urine test (41Ca assay) that can identify patients at very early stages of bone loss, as well as provide the means to monitor patients'responses to preventive drugs. These two pursuits will allow physicians to effectively treat high-risk patients early with preventive drugs, and monitor treatments'efficacy, which will improve patients'quality of life and reduce hospital costs.